Physicochemical principles of cardiovascular calcification

Objectives. The objectives of this review article are to provide detailed physicochemical information on the nature of pathological cardiovascular deposits, PCD, isolated from different sites of the human cardiovascular system. In order to help to understand the complex mechanism of the formation of PCD, special emphasis is focused on the attempt to recognize early precursor(s) of PCD by utilizing combined in vivo and in vitro studies. Background. The common idea is that PCD is hydroxyapatite (HAP), Ca5(PO4)3OH; however, this is questionable and deserves critical evaluation. Methods. After isolation of PCD, deproteination followed, producing pure inorganic fraction of deposits that were subject to chemical analyses, x-ray diffraction (XRD), FT-IR spectroscopy, optical, scanning electron microscopy (SEM), polarizing microscopy, energy dispersive x-ray microanalyses (EDS) and thermodynamic solubility measurements. The same methods were used to characterize the in vitro and in vivo formed calcific deposits. Results. The results of chemical analyses provided essential information that PCD contained significant organic fraction; inorganic fraction appears to be bioapatite, corresponding to defect HAP with substantial macro incorporation of sodium, magnesium, carbonate and fluoride. Structural XRD data show apatitic pattern; however, variable crystallinity of PCD suggests that crystallization is a time and flow dynamics-dependent process. Critical thermodynamic solubility measurements unequivocally prove that PCD are significantly more soluble than HAP. Conclusions. The PCDs are morphologically and chemically heterogeneous products which may be a consequence of time- dependent hydrolytic transformation of precursors that may include amorphous calcium phosphate and octacalcium phosphate (OCP) Ca4H(PO4)3.